Lyme borreliosis is now the most common arthropod-borne disease in the United States and Europe. It is caused by Borrelia burgdorferi, a tickborne spirochete that is related to the agents of relapsing fever. B. burgdorferi infection of adults and children is often complicated by chronic and disabling arthritis or neurologic disease. The immune response to the infection is characterized by the slow appearance of antibodies to abundant outer membrane proteins, known as Osp proteins, and by what may be an overly vigorous and self-injurous cell-mediated reaction. The role of spirochete components and virulence factors in either avoiding the antibody response or eliciting pathologic changes in the host is of interest. There is evidence of antigenic variation by B. burgdorferi both in vitro and in vivo. Study of diversity between strains and of antigenic variation of modulation within a strain may reveal critical factors in the pathogenesis of complicated Lyme borreliosis. Such a study may also identify potential vaccine candidates as well as reagents for improved diagnostic assays. The project will use a molecular genetic approach and will examine differences between strains and variants down to and including the level of the genome. The first specific aim of this project is characterization of differences between strains in their Osp and other surface proteins, in the structural protein of the spirochete's periplasmic flagella, and in a major 60K antigen. The second specific aim is determination of the mechanism of antigenic variation in B. burgdorferi. Important to this part of the study will be an investigation of the regulation of gene expression in B. burgdorferi.